Transcriptional dysfunction is an important pathologic factor associated in neurodegenerative diseases such as polyglutamine diseases. The present inventors have proved that polyglutamine diseases involve reduction of entire gene expression rather than reduction of expression of several particular genes (see, Non-Patent Literature 1). That is, a large number of transcription factors are known to co-localize or interact with mutant proteins that lead to polyglutamine diseases. A general transcription level, equivalent to an overall function level of transcription factors, is down-regulated by mutant polyglutamine protein. One of the major challenges to be tackled for the treatment of polyglutamine diseases is to unravel the relationship between transcriptional dysfunction and neuronal death. However, it is not certain whether inhibition of transcription triggers neuronal death. Also, the mechanism by which significant inhibition of transcription causes neuronal death remains totally elusive.
As described above, cellular transcriptional dysfunction is one of the major molecular-level causes of neurodegenerative diseases, particularly polyglutamine diseases. However, it is still unknown whether or not transcriptional dysfunction actually causes neuronal death and in what manner neuronal death occurs.
[Non-Patent Literature 1] BBRC, vol. 313, p110-116(2004)